Parasites lacking the micronemal protein MIC2 are deficient in surface attachment and host cell egress, but remain virulent in vivo.
Parasites lacking the micronemal protein MIC2 are deficient in surface attachment and host cell egress, but remain virulent in vivo.
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DOI：
10.12688/wellcomeopenres.11594.2
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发表时间：
2017
影响因子：
--
通讯作者：
Meissner M
中科院分区：
文献类型：
--
作者：
Gras S;Jackson A;Woods S;Pall G;Whitelaw J;Leung JM;Ward GE;Roberts CW;Meissner M
背景资料：血小板反应蛋白相关的无名蛋白（TRAP）家族的蛋白质被认为在顶复门寄生虫的滑行运动和宿主细胞入侵过程中发挥重要作用，目前代表了针对恶性疟原虫（疟疾的病原体）的主要疫苗候选物。然而，最近的证据表明，它们发挥的作用与以前的假设不同。在这里，我们分析了一个无效突变体MIC 2，TRAP同源弓形虫。研究方法：我们进行了仔细的分析寄生虫运动在3D环境中，附着在剪切应力条件下，宿主细胞入侵和体内毒力。结果如下：我们验证了MIC 2在有效表面附着中的作用，但无法鉴定MIC 2在维持滑行运动或宿主细胞入侵中的任何直接功能。此外，我们发现mic 2的缺失导致体内感染略微延迟，仅导致毒力轻度减弱;与野生型寄生虫一样，即使接种少量mic 2 KO寄生虫也会导致小鼠致死性疾病。然而，mic 2的缺失导致延迟的宿主细胞在体外的出口，可能通过破坏信号转导途径。结论：我们证实了MIC 2在寄生虫附着于表面中的关键作用，导致寄生虫运动和宿主细胞侵袭减少。然而，MIC 2似乎不是滑行运动或宿主细胞入侵的关键，因为寄生虫在这些过程中的速度不受影响。此外，MIC 2的缺失仅导致寄生虫的轻微减毒。
Background: Micronemal proteins of the thrombospondin-related anonymous protein (TRAP) family are believed to play essential roles during gliding motility and host cell invasion by apicomplexan parasites, and currently represent major vaccine candidates against Plasmodium falciparum, the causative agent of malaria. However, recent evidence suggests that they play multiple and different roles than previously assumed. Here, we analyse a null mutant for MIC2, the TRAP homolog in Toxoplasma gondii. Methods: We performed a careful analysis of parasite motility in a 3D-environment, attachment under shear stress conditions, host cell invasion and in vivo virulence. Results: We verified the role of MIC2 in efficient surface attachment, but were unable to identify any direct function of MIC2 in sustaining gliding motility or host cell invasion once initiated. Furthermore, we find that deletion of mic2 causes a slightly delayed infection in vivo, leading only to mild attenuation of virulence; like with wildtype parasites, inoculation with even low numbers of mic2 KO parasites causes lethal disease in mice. However, deletion of mic2 causes delayed host cell egress in vitro, possibly via disrupted signal transduction pathways. Conclusions: We confirm a critical role of MIC2 in parasite attachment to the surface, leading to reduced parasite motility and host cell invasion. However, MIC2 appears to not be critical for gliding motility or host cell invasion, since parasite speed during these processes is unaffected. Furthermore, deletion of MIC2 leads only to slight attenuation of the parasite.